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Human papillomavirus (HPV) infection in cervix is the most important reason for cervical cancer, but only 2% cervical HPV infection will develop into cervical cancer. So how to identify patients at risk of progressive cervical lesions from those infected with HPV to avoid over treatment is a big issue in clinic. The aims of this study were to detect the expression of HPV L1 capsid protein and p16INK4a in cervical lesions and to investigate the combination expression of HPV L1 capsid protein and p16INK4a in cervical lesions and its diagnostic efficiency in clinic. Immunochemical method was used to detect the expression of HPV L1 capsid protein and p16INK4a in 169 cases of abnormal cytology. Histopathologic test was performed to identify cervical lesions of all the cases. χ2 test and spearman's rank correlation were used for statistical analysis. The diagnostic sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), accuracy, and the area under the receive operating characteristic (ROC) curve (denoted by AZ) were calculated with SPSS 13.0. All the statistical tests were two sided at the 5% level of significance. L1 expression decreased (P < 0.001), but p16INK4a expression increased (P < 0.001) with histopathologic diagnosis increasing. The expression rates of HPV L1 capsid protein, p16INK4a, and L1(−)/p16(+) in cervical intraepithelial neoplasia (CIN)2, CIN3, and squamous-cell carcinoma were statistically different from those in CIN1 (P < 0.001). The expressions of HPV L1 capsid protein, L1(+)/p16(+), L1(+)/p16(−), and L1(−)/p16(−) were negatively correlated with the severity of cervical lesions (P < 0.001), whereas the expressions of p16INK4a and L1(−)/p16(+) were positively correlated with the severity of cervical lesions (P < 0.001). The specificity and AZ of combining L1 with p16 INK4a were statistically higher than L1 or p16 INK4a alone (P < 0.05). L1 and p16INK4a are useful biomarkers for the early diagnosis of cervical lesions. The combination of L1 and p16INK4a has a higher diagnostic accuracy than L1 or p16INK4a alone in diagnosis of cervical lesions. Diagn.